Cancer Medical Management Research Articles

Abstract 5062: Evaluation of genetic mutations in non-small cell lung cancer patients

Abstract Lung cancers represent the second most common cancer and Non-Small Cell Lung Cancer (NSCLC) constitutes 80-85% of all lung cancers. Genes within several cellular pathways have been previously evaluated for their clinical impact in NSCLC. In this investigation, we evaluate genetic mutations found in 50 cancer-critical genes implicated in the signaling pathways RTK/RAS/MAP, TGFβ, PI3K, Wnt, GPCR, p53, JAK/STAT, Notch, and the cell cycle pathway. Some of these mutations have not yet been described or have not been described in NSCLC. The intent of our study is to evaluate these mutations and allow further research into their impact, specifically highlighting mutations that are involved in clinically important pathways. We evaluated mutations found in 59 NSCLC patients at the Prisma Health Cancer Institute. These mutations are part of 2,800 COSMIC (Catalogue of Somatic Mutations in Cancer) hotspot mutations in 50 cancer-critical genes. Each mutation was investigated further using the ClinVar database to identify whether it had been described in NSCLC or other cancers/conditions, its genetic consequence, pathogenesis, possible variations, and origin. A total of 73 unique mutations in 59 NSCLC patients were evaluated. Of the 73 mutations, 17 had not been described at all, 40 had been described in other cancers/conditions, and 16 had been previously described in NSCLC. The known mutations’ effects in other cancers/conditions were categorized as pathogenic, likely pathogenic, likely benign, benign, or uncertain. Novel mutations were found in genes that provide a druggable target, help predict treatment response, are under investigation for their ability to predict treatment response or confer additional clinical utility. Medical management of cancer has benefitted greatly from studies of genetic mutations. Most mutations identified in our patient population had not been described in NSCLC, and a smaller number of those had not been described at all. Further elucidation of these mutations may lead to additional discoveries relevant to NSCLC prognostication and treatment. Citation Format: Miles Rothstein, Phillip Broughton, Ella Markalunas, Avery Funkhouser, Lorie Allen, Julie Martin, W. Jeffery Edenfield, Anna V. Blenda. Evaluation of genetic mutations in non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5062.

Landscape and Regulatory Perspective on Oncology Drugs in Pregnancy

AbstractCancers affecting pregnant women include breast cancer, melanoma, thyroid cancer, cervical cancer, lymphomas, and leukemias. The medical management of cancer during pregnancy with molecularly targeted oncology drugs remains quite challenging, with knowledge gaps about the drugs’ safety and efficacy due to exclusion of pregnant women from cancer clinical trials, discontinuation of individuals who become pregnant during clinical trials, and limited information on appropriate dosing of molecularly targeted oncology drugs during pregnancy. Physiological changes occur during pregnancy and may result in alterations in the absorption, distribution, metabolism, and excretion of drugs used in pregnant women. Physiologically based pharmacokinetic modeling that incorporates physiological changes induced by both the cancer disease state and pregnancy has the potential to inform dosing of molecularly targeted oncology drugs for pregnant women, improve our understanding of the pharmacokinetic changes associated with pregnancy in patients with cancer, facilitate the design of potential studies of molecularly targeted oncology drugs in pregnant women to support dosing recommendations, and provide model‐informed pharmacokinetic data to support regulatory decision making.

Postoperative quality-of-life assessment in patients with spine metastases treated with long-segment pedicle-screw fixation.

OBJECTIVE In recent decades, progress in the medical management of cancer has been significant, resulting in considerable extension of survival for patients with metastatic disease. This has, in turn, led to increased attention to the optimal surgical management of bone lesions, including metastases to the spine. In addition, there has been a shift in focus toward improving quality of life and reducing hospital stay for these patients, and many minimally invasive techniques have been introduced with the aim of reducing the morbidity associated with more traditional open approaches. The goal of this study was to assess the efficacy of long-segment percutaneous pedicle screw stabilization for the treatment of instability associated with thoracolumbar spine metastases in neurologically intact patients. METHODS This study was a retrospective review of data from a prospective database. The authors analyzed cases in which long-segment percutaneous pedicle screw fixation was performed for the palliative treatment of thoracolumbar spinal instability due to spinal metastases in neurologically intact patients. All of the patients included in the study underwent surgery between January 2014 and May 2015 at the authors' institution. Postoperative radiation therapy was planned within 10 days following the stabilization in all cases. Clinical and radiological follow-up assessments were planned for 3 days, 3 weeks, 6 weeks, 3 months, 6 months, and 1 year after surgery. Outcome was assessed by means of standard postoperative evaluation and oncological and spinal quality of life measures (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 [EORTC QLQ-C30] and Oswestry Disability Index [ODI], respectively). Moreover, 5 patients were given an activity monitoring device for recording the distance walked daily; preoperative and postoperative daily distances were compared. RESULTS Data from 17 cases were analyzed. There were no complications, and patients showed improvement in pain level and quality of life from the early postoperative period on. The mean ODI score was 62.7 (range 40-84) preoperatively, 35.4 (range 24-59) on postoperative Day 3, and 46.1 (range 30-76) at 3 weeks, 37.6 (range 25-59) at 6 weeks, 34.0 (range 24-59) at 3 months, 39.1 (range 22-64) at 6 months, and 30.0 (range 20-55) at 1 year after screw placement. The mean ODI was significantly improved in the first 45 days (p < 0.001). Improvement was also evident in scores for functional and symptomatic scales of the EORTC QLQ-C30. All patients underwent postoperative radiation therapy within 10 days (mean 7.5). All patients (n = 5) with an activity monitoring device showed improvement in daily walking distance. CONCLUSIONS Less-invasive palliative treatment for advanced spinal metastases is promising as part of a multidisciplinary approach to the care of patients with metastatic disease. The results of this study indicate that percutaneous surgery may allow for rapid improvement in quality of life and walking ability for patients with thoracolumbar instability due to spine metastases. Long-segment percutaneous screw fixation followed by early radiation therapy appears to be a safe and effective treatment option for providing solid and durable stability and improved quality of life for these patients.

The Influence of Treatment Facility Volume on Survival of Non-Hodgkin Lymphoma: Determining the Volume-Outcome Relationship

Background: Non-Hodgkin lymphoma (NHL) is a relatively uncommon cancer with annual incidence of ~70,000 cases but with over 50 distinct subtypes. The goal of this study was to determine the extent to which the number of NHL patients treated annually in a facility (facility volume) affects overall survival (OS). This study used the National Cancer Data Base (NCDB), a nationwide oncology database covering 70% of the US cancer population, to address this question.Methods: We used the NCDB to identify patients with NHL diagnosed from 1998 to 2006. Year 2006 was used as a cut-off in order to allow a minimum of five years of follow-up for all patients. Only patients treated at facilities with continuous annual reporting to NCDB were included. We classified treatment facilities by quartiles based on facility volume (mean patients/year): Quartile 1 (Q1: 2-13), Quartile 2 (Q2: 14-20), Quartile 3 (Q3: 21-32) and Quartile 4 (Q4: ≥33). We used Pearson correlation methods to examine collinearity, unadjusted Kaplan-Meier methods to estimate OS rates, log rank test to compare survival distributions, and multivariable Cox proportional hazards model to examine the associations between hospital volume and OS adjusting for other covariates of interest. We also included random effects for hospital to more fully adjust for clustering of outcomes within hospitals. To examine non-linear effects of hospital volume, we utilized smoothing splines.Results: There were 278,985 NHL patients cared for at 1,151 facilities. The distribution of patients according to facility volume was Q1 (10.7%), Q2 (13.5%), Q3 (23.3%) and Q4 (52.5%) and according to facility type was academic (31.2%), comprehensive community (55.9%), community (10.6%) and other (2.3%) centers. The unadjusted median OS by facility volume was: Q1: 61.8 months, Q2: 65.9 months, Q3: 71.4 months and Q4: 83.6 months. After multivariable analysis adjusting for demographic (sex, age, race, ethnicity), socioeconomic (income, insurance type), geographic (area of residence), disease-specific (NHL subtype, stage) and facility-specific (type and location) factors, we show that facility volume remains an independent predictor of all-cause mortality. Compared to patients treated at Q4 facilities, patients treated at lower quartile facilities had a worse OS (Q3HR: 1.05 [95% CI, 1.04-1.06]; Q2HR: 1.08 [1.07-1.10]; Q1HR: 1.14 [1.11-1.17]). We adjusted for hospital as a random effect, performed sensitivity analyses removing primary payor and facility type (due to collinearity with age and facility volume, respectively), and adjusted for Charlson-Deyo co-morbidity score (available only for patients diagnosed after 2003) in secondary models and found similar results. Using smoothing splines, we found a significant non-linear effect of hospital volume on OS (P <0.001). This is depicted in the Figure wherein the hazard ratio of 1.0 corresponded to the average predicted hazard, which occurred at a hospital volume of 59 patients per year.Conclusions: Patients who were treated for NHL at higher volume facilities had longer OS than those who were treated at facilities with a lower volume. This is the first study in the US using a national sample to show that a volume-outcome relationship exists in the medical management of cancer. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pharmacist–patient relationship is key in adherence to cancer meds

With the availability of more oral and topical drugs for the treatment of cancer, it's surprising to learn that adherence to cancer medication is a common problem among patients. "One of the thoughts that a lot of people had was that because cancer medicines are treating a life-threatening disease, patients would be much more certain to take medications as instructed," said J. Leonard Lichtenfeld, MD, MACP, Deputy Chief Medical Officer, American Cancer Society, in an interview with Pharmacy Today. But research has shown otherwise, according to Lichtenfeld. Adherence is a problem even though oral cancer drugs—such as the older and widely used tamoxifen, as well as newer oral drugs including aromatise inhibitors, imatinib mesylate, erlotinib, and capcetabine—have fewer adverse effects and are better tolerated than I.V. chemotherapy drugs. There is no "one size fits all" explanation for lack of adherence to medications that treat a life-threatening disease like cancer. Reasons cited include adverse effects that exist even with oral and topical drugs that are better tolerated, the cost of medications, a sense of fatalism about the disease, lack of support from family members and caregivers, and, especially among older adults who often take many medications, the difficulty in remembering to take their meds or in understanding how to take them correctly. At one time, only a handful of cancer medications were available for pharmacists to dispense for patients to take or use at home. With the approval of new oral and topical drugs and the changes in health care delivery, "cancer medication dispensed by pharmacists is going to become more the norm than the exception," Lichtenfeld said, adding that the key to ensuring adherence is developing a knowledgeable, caring relationship with patients. Pharmacists can help patients with cancer understand medication complexity, put systems in place to make sure patients are taking their medications, and give patients tools, such as simple checklists, to help them remember to take their medications. Pharmacists play a critical role "not just in dispensing medications but in checking the medications for errors, making sure patients understand directions, helping them understand the potential conflicts that exist with other medications or something the patient may be taking that the physician doesn't know about"—all very important parts of the larger patient care picture, Lichtenfeld said.A community pharmacist who "knows the patient, has a relationship with the patient, knows the patient's family" can reinforce the importance of taking medications correctly. These types of opportunities are more likely to exist in a well-established cancer center where, "in an ideal world," Lichtenfeld pointed out, pharmacists are part of the patient care team and make rounds with the physician. But a community pharmacist who has direct interaction with a patient—"who knows the patient, has a relationship with the patient, knows the patient's family"—can reinforce the importance of taking medications correctly and on a timely basis, he continued. "The [community] pharmacist can be part of that warning system that there may be a problem with that patient taking their medication, or there may be a problem with that patient being able to afford their medication," Lichtenfeld explained. "That becomes a situation where the pharmacist hopefully can interact with the care team that's providing the oncology treatment for that patient." Numerous resources are available to help patients adhere to their oral cancer medication regimen. For example, CancerCare offers free 1-hour podcasts, booklets, and fact sheets with information about the latest cancer treatments, managing side effects, and coping with cancer (www.cancercare.org). "The Importance of Taking Your Pills on Schedule: Understanding Adherence" and “Understanding the Important Role of Adherence in the Medical Management of Cancer" are two podcasts for patients with cancer. Booklets and fact sheets include "The Importance of Taking Your Pills Everyday on Schedule" and "The Importance of Taking Your Pills on Schedule." Patients with chronic myelogenous leukemia (CML) can turn to "Adherence and CML: Overcome the Challenges to Taking Your Pills" and "The Importance of Taking Your Prescribed Medication During Chronic Myelogenous Leukemia Treatment." The National Council on Patient Information and Education (NCPIE) offers Accelerating Progress in Prescription Medicine Adherence: The Adherence Action Agenda on its Be Medicine Smart website (www.bemedicinesmart.org). CDC's online medication adherence tools are also helpful (www.cdc.gov/primarycare/materials/medication/index.html).

Cancer in the elderly

A considerable knowledge has been collected in the last 20 years through retrospective and prospective trials on the medical management of cancer in older patients. Today a better approach to prevention and treatment of chemotherapy-related complications in older patients is provided by specific guide-lines.In this review, a synthetic information on the medical treatment specifically required by patients with age associated conditions for the most common tumor types (breast, non-small-cell lung prostate, colrectal cancer, and aggressive non-Hodgkin's lymphoma) is presented.

Towards In Vivo Imaging of Cancer Sialylation

In vivo assessment of tumor glucose catabolism by positron emission tomography (PET) has become a highly valued study in the medical management of cancer. Emerging technologies offer the potential to evaluate in vivo another aspect of cancer carbohydrate metabolism related to the increased anabolic use of monosaccharides like sialic acid (Sia). Sia is used for the synthesis of sialylated oligosaccharides in the cell surface that in cancer cells are overexpressed and positively associated to malignancy and worse prognosis because of their role in invasion and metastasis. This paper addresses the key points of the different strategies that have been developed to image Sia expression in vivo and the perspectives to translate it from the bench to the bedside where it would offer the clinician highly valued complementary information on cancer carbohydrate metabolism that is currently unavailable in vivo.

Clinical Oncology—Basic Principles and Practice, 3rd edition

Clinical Oncology—Basic Principles and Practice, 3rd edition

The Medical Management of Cancer.

The subject material in this well-documented text is based on and presented from considerable personal experience by the author from his work at the Memorial Center for Cancer and Allied Diseases, New York. The foreword endorsement by Lloyd F. Cramer, M.D., adds prestige. This monograph is divided into two sections and an appendix. The first section deals with cancers where the primary treatment is medical (nonsurgical); this first section covers the malignant lymphomas, the leukemias, and plasma-cell myeloma. The second section discusses the medical management where the primary treatment is surgical—neuroblastoma, cancer of the lung, thyroid, ovary, breast, and prostate. A final section, or appendix, reviews the literature and presents the experience at the Memorial Center on the intracavity use of injectable radioisotopes. The appendix was edited by the author but was prepared by Richard Y. Card, M.D., and Ulrich K. Henschke, M.D. The index and bibliography are satisfactory. The

The Medical Management of Cancer

The Medical Management of Cancer

The Medical Management of Cancer

The Medical Management of Cancer